1. DEFER STUDY: 5-YEAR FOLLOW-UP A Multicenter Randomized Study
to Compare Deferral Versus Performance of PCI
of Non-Ischemia-Producing Stenoses
Principal investigators
Nico H.J. Pijls, MD, PhD
Catharina Hospital
Eindhoven, The Netherlands
Bernard De Bruyne, MD, PhD
Cardiovascular Center Aalst
Aalst, Belgium

2. NOTE
Any treatment in health care should be directed
either to
Releave symptoms ( improve functional class )
or to
Improve outcome ( prognosis, longevity)
No other justification for any treatment is possible !

3. and prognosis (outcome)
DEFER study: background (1)
In patients with coronary artery disease,
the most important factor with respect to both
functional class (symptoms)
and prognosis (outcome)
Is the presence and extent of inducible ischemia
(many invasive & non-invasive studies in > 100,000 patients)
If a stenosis is responsible for reversible
ischemia, revascularization improves symptoms
(if present) and outcome…..

4. DEFER study: background (2)
If a stenosis is responsible for reversible
ischemia, revascularization is justified……
……But what if a stenosis or “plaque” is
NOT responsible for reversible ischemia ?
(functionally “non-significant” , “non-culprit”)
PCI is often performed in such lesions,
yet the benefit of such treatment is not clear

5. 158 vb38/interm.RCA/Buddem (1)
female, 58-y-old
underwent PCI of severe LCX lesion a minute before
50 % stenosis in mid RCA
Should this lesion be stented ??
158 vb38/interm.RCA/Buddem (1)

6. DEFER study: background (3)
Fractional Flow Reserve, calculated from
coronary pressure measurement, is an accurate,
invasive, and lesion-specific index to demonstrate
or exclude whether a particular coronary stenosis
can cause reversible ischemia.
FFR can be determined easily, in the cath-lab,
immediately prior to a planned intervention
FFR based strategy for PCI in equivocal stenosis
( DEFER – Study)

7. prospective randomized multicentric trial
The DEFER Study: Design
prospective randomized multicentric trial
(14 centers) in 325 patients with stable
chest pain and an intermediate stenosis
without objective evidence of ischemia
Aalst
Amsterdam
Eindhoven
Essen
Gothenborg Hamburg
Liège
Maastricht
Madrid
Osaka
Rotterdam
Seoul
Utrecht
Zwolle
data collection & analysis:
Jan Willem Bech, MD, PhD
Pepijn van Schaardenburgh, MD

8. The DEFER Study: Objectives
Primary objective
to test safety of deferring PCI of stenoses
not responsible for inducible ischemia as
indicated by FFR > 0.75 ( “outcome” )
Secondary objective
to compare quality of life in such patients,
whether or not treated by PCI
(CCS-class, need for anti-anginal drugs)
(“symptoms”)

9. Patients scheduled for PCI without Proof of Ischemia (n=325)
The DEFER Study: Flow Chart
Patients scheduled for PCI without Proof of Ischemia (n=325)
Randomization
deferral of PTCA
(167)
performance of PTCA (158)
FFR < 0.75
(68)
PTCA
FFR  0.75
(91)
FFR < 0.75
(76)
FFR  0.75
(90)
No PTCA
PTCA
PTCA
DEFER Group
REFERENCE Group
PERFORM Group

10. THE DEFER STUDY: RANDOMIZATION
deferral of PCI
performance of PCI
1 : 1 randomization
If FFR < performance anyway
reference group
If FFR > randomization followed
defer PCI perform PCI

11. The DEFER Study: Catheterization
6 or 7 F guiding catheter for measurement of
aortic pressure ( Pa)
QCA from 2 orthogonal views
Coronary pressure measurement (Pd ) by
0.014” pressure wire (Radi Medical Systems)
Maximum hyperemia by i.v. adenosine (140 ug/kg/min)
Calculation of Fractional Flow Reserve by:
FFR = Pd / Pa

12. The DEFER Study: Base line data
Randomized to Randomized to
Deferral of PTCA Performance of PTCA
N= N=158
Age, (yr) 62 10
Female sex (%)
Ejection Fraction (%) 67 9
Diabetes (%)
Hypertension (%)
Hyperlipidemia (%)
Current Smoker (%)
Family History CAD (%)

13. The DEFER Study: Baseline QCA and FFR
Ref. diam. (mm) ± ± 0.57
MLD (mm) ± 0.40
DS (%) ± 10
1.42 ± 0.38
52 ± 11
Randomized to Randomized to
Deferral of PTCA Performance of PTCA
N= N=158
FFR 0.19
0.730.19
All baseline characteristics were identical between both groups

14. Diameter Stenosis versus FFR
The DEFER Study:
Diameter Stenosis versus FFR

15. event – free survival (%)
100 75
78.8
72.7
64.4 50
Defer
p=0.52
Perform
p=0.03
p=0.17 25
Reference
(FFR < 0.75) 1 2 3 4 5
Years of Follow-up
No. at risk
Defer group 90 85 82 74 73 72
Perform group 88 78 70 67 65
Reference gr
135
105
103 96

16. DEFER: Clinical Outcome at 5 Years
FFR ≥0.75
FFR<0.75
Defer
Perform
Reference
Number of patients 91 90
144
Lost to follow-up
Cardiac Death(%)
3 (3.3)
2 (2.3)
8 (6.0)
Non Cardiac Death(%)
3 (3.3)
3 (3.4)
4 (3.0)
Q wave MI (%)
4 (4.5)
6 (4.5)
Non-Q wave MI(%)
1 (1.1)
7 (5.2)
CABG(%)
1 (1.1)
4 (4.5)
14 (10.4)
TLR(%)
8 (8.9)
8 (9.1)
18 (13.4)
11 (8.2)
6 (6.8)
6 (6.7)
Non-TLR(%)
Other (%)
1 (1.1)
2 (1.5)
Total events 21 29 70
52 (39 %)
24 (27 %)
19 (21 %)
Patients ≥1 event (%)
Pts free of angina(%)
68 %
58 %
72 %

17. Cardiac Death And Acute MI After 5 Years
P< 0.03 % 20
P< 0.005
15.7 15
P=0.20 10
7.9 5
3.3
DEFER PERFORM REFERENCE
FFR > FFR < 0.75

18. freedom from chest pain
100% *
* *
* *
80%
* * *
60%
40%
20% 0%
baseline
1month
1 year
2 year
5 year
Defer group
Perform group
Reference group
FFR > FFR > FFR < 0.75

19. DEFER: Summary and Conclusions (1)
In patients with stable chest pain, the most important prognostic factor of a given coronary artery stenosis, is its ability of inducing myocardial ischemia (as reflected by FFR < 0.75)
In those patients, clinical outcome of such “ischemic” stenosis, even when treated by PCI, is much worse than that of a functionally “non-significant” stenosis.
3. The prognosis of “non-ischemic” stenosis (FFR > 0.75) is excellent and the risk of such “non-significant” stenosis or plaque to cause death or AMI is < 1% per year, and not decreased by stenting

20. DEFER: Summary and Conclusions (2)
Stenting a “non-ischemic” stenosis does not benefit patients with stable chest pain, neither
in prognostic nor symptomatic respect.

21. event – free survival (%)
100
75.8 75
64.4 50
FFR
0.75
p=0.03
FFR < 0.75 25 1 2 3 4 5
Years of Follow-up
No. at risk
FFR ≥ 0.75
178
162
154
143
138
136
FFR < 0.75
135
105
103 96 90 88